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Immune checkpoint modulation enhances HIV-1 antibody induction.

Authors :
Bradley, Todd
Kuraoka, Masayuki
Yeh, Chen-Hao
Tian, Ming
Chen, Huan
Cain, Derek W.
Chen, Xuejun
Cheng, Cheng
Ellebedy, Ali H.
Parks, Robert
Barr, Maggie
Sutherland, Laura L.
Scearce, Richard M.
Bowman, Cindy M.
Bouton-Verville, Hilary
Santra, Sampa
Wiehe, Kevin
Lewis, Mark G.
Ogbe, Ane
Borrow, Persephone
Source :
Nature Communications; 2/19/2020, Vol. 11 Issue 1, p1-16, 16p
Publication Year :
2020

Abstract

Eliciting protective titers of HIV-1 broadly neutralizing antibodies (bnAbs) is a goal of HIV-1 vaccine development, but current vaccine strategies have yet to induce bnAbs in humans. Many bnAbs isolated from HIV-1-infected individuals are encoded by immunoglobulin gene rearrangments with infrequent naive B cell precursors and with unusual genetic features that may be subject to host regulatory control. Here, we administer antibodies targeting immune cell regulatory receptors CTLA-4, PD-1 or OX40 along with HIV envelope (Env) vaccines to rhesus macaques and bnAb immunoglobulin knock-in (KI) mice expressing diverse precursors of CD4 binding site HIV-1 bnAbs. CTLA-4 blockade augments HIV-1 Env antibody responses in macaques, and in a bnAb-precursor mouse model, CTLA-4 blocking or OX40 agonist antibodies increase germinal center B and T follicular helper cells and plasma neutralizing antibodies. Thus, modulation of CTLA-4 or OX40 immune checkpoints during vaccination can promote germinal center activity and enhance HIV-1 Env antibody responses. Elucidation of broadly neutralizing antibodies (bnAb) is a goal in HIV vaccine development. Here, Bradley et al. show that administration of CTLA-4 blocking antibody with vaccine antigens increases HIV-1 envelope antibody responses in macaques and a bnAb precursor mouse model. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
20411723
Volume :
11
Issue :
1
Database :
Complementary Index
Journal :
Nature Communications
Publication Type :
Academic Journal
Accession number :
141826904
Full Text :
https://doi.org/10.1038/s41467-020-14670-w